The Therapeutic Effects of Dodecaborate Containing Boronophenylalanine for Boron Neutron Capture Therapy in a Rat Brain Tumor Model
Yusuke Fukuo,
Yoshihide Hattori,
Shinji Kawabata,
Hideki Kashiwagi,
Takuya Kanemitsu,
Koji Takeuchi,
Gen Futamura,
Ryo Hiramatsu,
Tsubasa Watanabe,
Naonori Hu,
Takushi Takata,
Hiroki Tanaka,
Minoru Suzuki,
Shin-Ichi Miyatake,
Mitsunori Kirihata,
Masahiko Wanibuchi
Affiliations
Yusuke Fukuo
Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
Yoshihide Hattori
Research Center of Boron Neutron Capture Therapy, Research Organization for the 21st Century, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai-shi, Osaka 599-8531, Japan
Shinji Kawabata
Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
Hideki Kashiwagi
Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
Takuya Kanemitsu
Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
Koji Takeuchi
Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
Gen Futamura
Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
Ryo Hiramatsu
Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
Tsubasa Watanabe
Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2 Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan
Naonori Hu
Kansai BNCT Medical Center, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
Takushi Takata
Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2 Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan
Hiroki Tanaka
Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2 Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan
Minoru Suzuki
Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2 Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan
Shin-Ichi Miyatake
Kansai BNCT Medical Center, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
Mitsunori Kirihata
Research Center of Boron Neutron Capture Therapy, Research Organization for the 21st Century, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai-shi, Osaka 599-8531, Japan
Masahiko Wanibuchi
Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan
Background: The development of effective boron compounds is a major area of research in the study of boron neutron capture therapy (BNCT). We created a novel boron compound, boronophenylalanine–amide alkyl dodecaborate (BADB), for application in BNCT and focused on elucidating how it affected a rat brain tumor model. Methods: The boron concentration of F98 rat glioma cells following exposure to boronophenylalanine (BPA) (which is currently being utilized clinically) and BADB was evaluated, and the biodistributions in F98 glioma-bearing rats were assessed. In neutron irradiation studies, the in vitro cytotoxicity of each boron compound and the in vivo corresponding therapeutic effect were evaluated in terms of survival time. Results: The survival fractions of the groups irradiated with BPA and BADB were not significantly different. BADB administered for 6 h after the termination of convection-enhanced delivery ensured the highest boron concentration in the tumor (45.8 μg B/g). The median survival time in the BADB in combination with BPA group showed a more significant prolongation of survival than that of the BPA group. Conclusion: BADB is a novel boron compound for BNCT that triggers a prolonged survival effect in patients receiving BNCT.
